Diet and primary prevention of stroke: Systematic review and dietary recommendations by the ad hoc Working Group of the Italian Society of Human Nutrition.

BACKGROUND AND AIMS: To systematically review the latest evidence on established and emerging nutrition-related risk factors for incidence of and mortality from total, ischemic and haemorrhagic strokes. The present review was conducted in the framework of the work carried out through 2015 and 2016 for the preparation of the Italian Guidelines for the Prevention and Treatment of Stroke, 8th Edition, by ISO-SPREAD (Italian Stroke Organization and the Stroke Prevention and Educational Awareness Diffusion). METHODS AND RESULTS: Systematic review of articles focused on primary prevention of stroke published between January 2013 to May 2016 through an extensive search of the literature using MEDLINE/PUBMED, EMBASE and the Cochrane Library. Articles were ranked according to the SIGN methodology while the GRADE system was used to establish the strength of recommendations. As a result of our literature search, we examined 87 meta-analyses overall (mainly of prospective studies), a few isolated more recent prospective studies not included in the meta-analyses, and a smaller number of available randomized controlled trials and case-control studies. Based on the analysis of the above articles, 36 Syntheses of the available evidence and 36 Recommendations were eventually prepared. The present document was developed by organizing the available evidence into three individual areas (nutrients, food groups and dietary patterns) to provide a systematic and user-friendly overview of the available evidence on the relationship between nutrition and primary prevention of stroke. Yet analysis of foods and food patterns allowed translating the information about nutrients in a tool more amenable to use in daily life also in the light of the argument that people eat foods rather than nutrients. CONCLUSIONS: The present literature review and dietary recommendations provide healthcare professionals and all interested readers with a useful overview for the reduction of the risk of total, ischemic and haemorrhagic stroke through dietary modifications.

Relationship Between Cortical Gyrification, White Matter Connectivity, and Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition, which is accompanied by differences in gray matter neuroanatomy and white matter connectivity. However, it is unknown whether these differences are linked or reflect independent aetiologies. Using a multimodal neuroimaging approach, we therefore examined 51 male adults with ASD and 48 neurotypical controls to investigate the relationship between gray matter local gyrification (lGI) and white matter diffusivity in associated fiber tracts. First, ASD individuals had a significant increase in gyrification around the left pre- and post-central gyrus. Second, white matter fiber tracts originating and/or terminating in the cluster of increased lGI had a significant increase in axial diffusivity. This increase in diffusivity was predominantly observed in tracts in close proximity to the cortical sheet. Last, we demonstrate that the increase in lGI was significantly correlated with increased diffusivity of short tracts. This relationship was not significantly modulated by a main effect of group (i.e., ASD), which was more closely associated with gray matter gyrification than white matter diffusivity. Our findings suggest that differences in gray matter neuroanatomy and white matter connectivity are closely linked, and may reflect common rather than distinct aetiological pathways.

From Phineas Gage and Monsieur Leborgne to H.M.: Revisiting Disconnection Syndromes.

On the 50th anniversary of Norman Geschwind's seminal paper entitled 'Disconnexion syndrome in animal and man', we pay tribute to his ideas by applying contemporary tractography methods to understand white matter disconnection in 3 classic cases that made history in behavioral neurology. We first documented the locus and extent of the brain lesion from the computerized tomography of Phineas Gage's skull and the magnetic resonance images of Louis Victor Leborgne's brain, Broca's first patient, and Henry Gustave Molaison. We then applied the reconstructed lesions to an atlas of white matter connections obtained from diffusion tractography of 129 healthy adults. Our results showed that in all 3 patients, disruption extended to connections projecting to areas distant from the lesion. We confirmed that the damaged tracts link areas that in contemporary neuroscience are considered functionally engaged for tasks related to emotion and decision-making (Gage), language production (Leborgne), and declarative memory (Molaison). Our findings suggest that even historic cases should be reappraised within a disconnection framework whose principles were plainly established by the associationist schools in the last 2 centuries.

Frontotemporal white-matter microstructural abnormalities in adolescents with conduct disorder: a diffusion tensor imaging study.

BACKGROUND: Children with conduct disorder (CD) are at increased risk of developing antisocial personality disorder (ASPD) and psychopathy in adulthood. The biological basis for this is poorly understood. A preliminary diffusion tensor magnetic resonance imaging (DT-MRI) study of psychopathic antisocial adults reported significant differences from controls in the fractional anisotropy (FA) of the uncinate fasciculus (UF), a white-matter tract that connects the amygdala to the frontal lobe. However, it is unknown whether developmental abnormalities are present in the UF of younger individuals with CD. METHOD: We used DT-MRI tractography to investigate, for the first time, the microstructural integrity of the UF in adolescents with CD, and age-related differences in this tract. We compared FA and perpendicular diffusivity of the UF in 27 adolescents with CD and 16 healthy controls (12 to 19 years old) who did not differ significantly in age, IQ or substance use history. To confirm that these findings were specific to the UF, the same measurements were extracted from two non-limbic control tracts. Participants in the CD group had a history of serious aggressive and violent behaviour, including robbery, burglary, grievous bodily harm and sexual assault. RESULTS: Individuals with CD had a significantly increased FA (p = 0.006), and reduced perpendicular diffusivity (p = 0.002), in the left UF. Furthermore, there were significant age-related between-group differences in perpendicular diffusivity of the same tract (Z obs = 2.40, p = 0.01). Controls, but not those with CD, showed significant age-related maturation. There were no significant between-group differences in any measure within the control tracts. CONCLUSIONS: Adolescents with CD have significant differences in the 'connectivity' and maturation of UF.

Assay of CB1 Receptor Binding.

Type-1 cannabinoid receptor (CB1), one of the main targets of endocannabinoids, plays a key role in several pathophysiological conditions that affect both the central nervous system and peripheral tissues. Today, its biochemical identification and pharmacological characterization, as well as the screening of thousands of novel ligands that might be useful for developing CB1-based therapies, are the subject of intense research. Among available techniques that allow the analysis of CB1 binding activity, radioligand-based assays represent one of the best, fast, and reliable methods.Here, we describe radioligand binding methods standardized in our laboratory to assess CB1 binding in both tissues and cultured cells. We also report a high-throughput radioligand binding assay that allows to evaluate efficacy and potency of different compounds, which might represent the basis for the development of new drugs that target CB1-dependent human diseases.

DNA-Protein-Interaction (DPI)-ELISA Assay for PPAR-γ Receptor Binding.

Dysregulation of peroxisome proliferator-activated receptor (PPAR)-γ has been described in a plethora of pathological conditions, such as diabetes, obesity, inflammatory-related diseases, and cancer. Therefore, identifying novel drugs that are able to restore PPAR-γ activity is a current challenge, which is however slowed down by the lack of a rapid and reproducible activity assay. To date, only a few methods are able to characterize PPAR-γ activity and most of them are expensive, time-consuming, and not always quantitative.Herein, we presented a sensitive multi-well colorimetric assay, termed DNA-Protein-Interaction enzyme-linked immunosorbent assay (DPI-ELISA). This method is based on the ELISA principle, except that it allows to detect only activated PPAR-γ because, unlike classical ELISA, PPAR-γ is not captured by an antibody but by a double-stranded oligonucleotide probe containing its peroxisome proliferator response elements (PPRE) consensus sequence. Thus, DPI-ELISA represents a useful assay for PPAR-γ studies, as well as for the identification of novel PPAR-γ ligands for the development of innovative therapeutic approaches to human diseases where PPAR-γ signaling is dysregulated.

Octogenarians: an increasing challenge for acute care and colorectal surgeons. An outcomes analysis of emergency colorectal surgery in the elderly.

AIM: Emergency surgery is associated with higher mortality rates, especially in elderly patients presenting with emergent colorectal disease. The aim of this study was to determine the outcomes in elderly patients following emergency colorectal resection, with particular focus on octogenarians who presented a sixfold higher mortality rate with respect to other patients. METHOD: This study examined 355 patients who underwent surgery at an Emergency Department for complications of colorectal disease between January 2007 and December 2009. Morbidity and mortality were analyzed on the basis of patients' characteristics and presentation. Univariate and logistic regression analyses were performed on morbidity and mortality risk factors. RESULTS: Two-hundred and fifteen patients of > 65 years of age were included, 93 of whom were ≥ 80 years of age. The global mortality rate was 16%. In patients ≥ 80 years of age the mortality rate was 30%. The difference in mortality rate between patients < 80 years of age vs patients ≥ 80 years of age was 24%. In resected patients ≥ 80 years of age, American Society of Anesthesiology grade, colonic ischaemia, neurological comorbidity and anastomotic dehiscence were identified as independent risk factors in both univariate and logistic regression analyses. The morbidity rate was approximately 17%, and no significant difference in morbidity was found between the two groups. CONCLUSION: The results of this study show that fitness status and micro vascular impairment impact significantly on mortality in the elderly, particularly in octogenarians. Although the outcomes observed were compatible with the literature, the six fold higher mortality rate observed in the most elderly patients identifies a group for which death prevention is best achieved with aggressive resuscitation and intensive postoperative care, rather than timing of surgery.

Laparoscopic adhesiolysis: consensus conference guidelines.

AIM: Laparoscopic adhesiolysis has been demonstrated to be technically feasible in small bowel obstruction and carries advantages in terms of post-surgical course. The increasing dissemination of laparoscopic surgery in the emergency setting and the lack of concrete evidence in the literature have called for a consensus conference to draw recommendations for clinical practice. METHODS: A literature search was used to outline the evidence, and a consensus conference was held between experts in the field. A survey of international experts added expertise to the debate. A public jury of surgeons discussed and validated the statements, and the entire process was reviewed by three external experts. RESULTS: Recommendations concern the diagnostic evaluation, the timing of the operation, the selection of patients, the induction of the pneumoperitoneum, the removal of the cause of obstructions, the criteria for conversion, the use of adhesion-preventing agents, the need for high-technology dissection instruments and behaviour in the case of misdiagnosed hernia or the need for bowel resection. CONCLUSION: Evidence of this kind of surgery is scanty because of the absence of randomized controlled trials. Nevertheless laparoscopic skills in emergency are widespread. The recommendations given with the consensus process might be a useful tool in the hands of surgeons.

Differential corticospinal tract degeneration in homozygous 'D90A' SOD-1 ALS and sporadic ALS.

BACKGROUND: The homogeneous genotype and stereotyped phenotype of a unique familial form of amyotrophic lateral sclerosis (ALS) (patients homozygous for aspartate-to-alanine mutations in codon 90 (homD90A) superoxide dismutase 1) provides an ideal model for studying genotype/phenotype interactions and pathological features compared with heterogeneous apparently sporadic ALS. The authors aimed to use diffusion tensor tractography to quantify and compare changes in the intracerebral corticospinal tracts of patients with both forms of ALS, building on previous work using whole-brain voxelwise group analysis. METHOD: 21 sporadic ALS patients, seven homD90A patients and 20 healthy controls underwent 1.5 T diffusion tensor MRI. Patients were assessed using 'upper motor neuron burden,' El Escorial and ALSFR-R scales. The intracranial corticospinal tract was assessed using diffusion tensor tractography measures of fractional anisotropy (FA), mean diffusivity, and radial and axial diffusivity obtained from its entire length. RESULTS: Corticospinal tract FA was reduced in sporadic ALS patients compared with both homD90A ALS patients and controls. The diffusion measures in sporadic ALS patients were consistent with anterograde (Wallerian) degeneration of the corticospinal tracts. In sporadic ALS, corticospinal tract FA was related to clinical measures. Despite a similar degree of clinical upper motor neuron dysfunction and disability in homD90A ALS patients compared with sporadic ALS, there were no abnormalities in corticospinal tract diffusion measures compared with controls. CONCLUSIONS: Diffusion tensor tractography has shown axonal degeneration within the intracerebral portion of the corticospinal tract in sporadic ALS patients, but not those with a homogeneous form of familial ALS. This suggests significant genotypic influences on the phenotype of ALS and may provide clues to slower progression of disease in homD90A patients.

Voxel-based meta-analysis of regional white-matter volume differences in autism spectrum disorder versus healthy controls.

BACKGROUND: We conducted a meta-analysis of voxel-based morphometry (VBM) studies in autism spectrum disorder (ASD) to clarify the changes in regional white-matter volume underpinning this condition, and generated an online database to facilitate replication and further analyses by other researchers. METHOD: PubMed, ScienceDirect, Web of Knowledge and Scopus databases were searched between 2002 (the date of the first white-matter VBM study in ASD) and 2010. Manual searches were also conducted. Authors were contacted to obtain additional data. Coordinates were extracted from clusters of significant white-matter difference between patients and controls. A new template for white matter was created for the signed differential mapping (SDM) meta-analytic method. A diffusion tensor imaging (DTI)-derived atlas was used to optimally localize the changes in white-matter volume. RESULTS: Thirteen datasets comprising 246 patients with ASD and 237 healthy controls met inclusion criteria. No between-group differences were found in global white-matter volumes. ASD patients showed increases of white-matter volume in the right arcuate fasciculus and also in the left inferior fronto-occipital and uncinate fasciculi. These findings remained unchanged in quartile and jackknife sensitivity analyses and also in subgroup analyses (pediatric versus adult samples). CONCLUSIONS: Patients with ASD display increases of white-matter volume in tracts known to be important for language and social cognition. Whether the results apply to individuals with lower IQ or younger age and whether there are meaningful neurobiological differences between the subtypes of ASD remain to be investigated.

Redox modulation of Ecto-NOX1 in human platelets.

By modulating the cellular redox state, the plasma membrane electron transport (PMET) is important in platelet biology; indeed, the oxidant/antioxidant balance plays a central role during activation of the coagulation pathway. None the less, in human platelets, the PMET system has not yet been fully characterized and the molecular identities of most components are unknown. Here, for the first time, the presence of the plasma membrane hydroquinone (NADH) oxidase Ecto-NOX1 in human platelets has been described. We found that Ecto-NOX1 expression is modulated by capsaicin: Indeed, it is positively regulated through a mechanism requiring binding of capsaicin to its receptor, namely the transient receptor potential vanilloid subtype 1 (TRPV1). Ligand-receptor interaction triggers a signalling cascade leading to ROS production, which in turn enhances expression and activity of Ecto-NOX1. Redox regulation of Ecto-NOX1 may be important to platelet recruitment and activation during inflammatory diseases.

Ectopic liver nodules: a rare finding during cholecystectomy.

The ectopic liver (or choristoma) is a rare condition found during autopsy or abdominal exploration for various indications. The authors report two cases of ectopic liver found during laparoscopic cholecystectomy for acute cholestytis. The ectopic liver tissue has been reported to develop in several sites as thoracic cavity, gastrohepatic ligament, adrenal glands, pancreas, esophagus and, above all, gallbladder. The Authors review the literature and report their experience as a contribution to the knowledge of this rare pathological entity.

New immunological potential markers for triple negative breast cancer: IL18R1, CD53, TRIM, Jaw1, LTB, PTPRCAP.

Breast cancer (BC) is the second leading cause of cancer death in women worldwide, and settings of specific prognostic factors and efficacious therapies are made difficult by phenotypic heterogeneity of BC subtypes. Therefore, there is a current urgent need to define novel predictive genetic predictors that may be useful for stratifying patients with distinct prognostic outcomes. Here, we looked for novel molecular signatures for triple negative breast cancers (TNBCs). By a bioinformatic approach, we identified a panel of genes, whose expression was positively correlated with disease-free survival in TNBC patients, namely IL18R1, CD53, TRIM, Jaw1, LTB, and PTPRCAP, showing specific immune expression profiles linked to survival prediction; most of these genes are indeed expressed in immune cells and are required for productive lymphocyte activation. According to our hypothesis, these genes were not, or poorly, expressed in different TNBC cell lines, derived from either primary breast tumours or metastatic pleural effusions. This conclusion was further supported in vivo, as immuno-histochemical analysis on biopsies of TNBC invasive ductal carcinomas highlighted differential expression of these six genes in cancer cells, as well as in intra- and peri-tumoral infiltrating lymphocytes. Our data open to the possibility that inter-tumour heterogeneity of immune markers might have predictive value; further investigations are recommended in order to establish the real power of cancer-related immune profiles as prognostic factors.

Disorders of visual perception.

Visual perceptual disorders are often presented as a disparate group of neurological deficits with little consideration given to the wide range of visual symptoms found in psychiatric and neurodevelopmental disease. Here, the authors attempt a functional anatomical classification of all disorders linked to visual perception, whatever the clinical context in which they arise, including those disorders that bridge vision, emotion, memory, language and action. Guided by clinical and neuroimaging evidence, visual perceptual disorders are classified by the functional anatomical networks likely to be involved and the class of underlying dysfunction, whether topological (a localised deficit or region of hyperfunction) or hodological (a disconnection or hyperconnection). The wider perspective forces us to consider what visual functions underlie a range of symptoms sidelined by previous classificatory schemes and helps generate novel hypotheses for further research in the area.

Altered connections on the road to psychopathy.

Psychopathy is strongly associated with serious criminal behaviour (for example, rape and murder) and recidivism. However, the biological basis of psychopathy remains poorly understood. Earlier studies suggested that dysfunction of the amygdala and/or orbitofrontal cortex (OFC) may underpin psychopathy. Nobody, however, has ever studied the white matter connections (such as the uncinate fasciculus (UF)) linking these structures in psychopaths. Therefore, we used in vivo diffusion tensor magnetic resonance imaging (DT-MRI) tractography to analyse the microstructural integrity of the UF in psychopaths (defined by a Psychopathy Checklist Revised (PCL-R) score of > or = 25) with convictions that included attempted murder, manslaughter, multiple rape with strangulation and false imprisonment. We report significantly reduced fractional anisotropy (FA) (P<0.003), an indirect measure of microstructural integrity, in the UF of psychopaths compared with age- and IQ-matched controls. We also found, within psychopaths, a correlation between measures of antisocial behaviour and anatomical differences in the UF. To confirm that these findings were specific to the limbic amygdala-OFC network, we also studied two 'non-limbic' control tracts connecting the posterior visual and auditory areas to the amygdala and the OFC, and found no significant between-group differences. Lastly, to determine that our findings in UF could not be totally explained by non-specific confounds, we carried out a post hoc comparison with a psychiatric control group with a past history of drug abuse and institutionalization. Our findings remained significant. Taken together, these results suggest that abnormalities in a specific amygdala-OFC limbic network underpin the neurobiological basis of psychopathy.

Platelet Responses in Cardiovascular Disease: Sex-Related Differences in Nutritional and Pharmacological Interventions.

Cardiovascular diseases (CVD) represent one of the biggest causes of death globally, and their prevalence, aetiology, and outcome are related to genetic, metabolic, and environmental factors, among which sex- and age-dependent differences may play a key role. Among CVD risk factors, platelet hyperactivity deserves particular mention, as it is involved in the pathophysiology of main cardiovascular events (including stroke, myocardial infarction, and peripheral vascular injury) and is closely related to sex/age differences. Several determinants (e.g., hormonal status and traditional cardiovascular risk factors), together with platelet-related factors (e.g., plasma membrane composition, receptor signaling, and platelet-derived microparticles) can elucidate sex-related disparity in platelet functionality and CVD onset and outcome, especially in relation to efficacy of current primary and secondary interventional strategies. Here, we examined the state of the art concerning sex differences in platelet biology and their relationship with specific cardiovascular events and responses to common antiplatelet therapies. Moreover, as healthy nutrition is widely recognized to play a key role in CVD, we also focused our attention on specific dietary components (especially polyunsaturated fatty acids and flavonoids) and patterns (such as Mediterranean diet), which also emerged to impact platelet functions in a sex-dependent manner. These results highlight that full understanding of gender-related differences will be useful for designing personalized strategies, in order to prevent and/or treat platelet-mediated vascular damage.

The plasma membrane redox system in human platelet functions and platelet-leukocyte interactions.

The plasma membrane electron transport is crucial for blood coagulation and thrombosis, since reactive oxygen species and thiol changes, generated by plasma membrane redox reactions, modulate activation of platelets, as well as their interaction with leukocytes. Several antioxidants are linked to this system; thus, platelets are also able to counterbalance radical production and to regulate thrombus growth. Aim of this review is to give an update on the plasma membrane redox system in platelets, as well as on its role in platelet functions and leukocyte-platelet cross-talk.

Brain networks of spatial awareness: evidence from diffusion tensor imaging tractography.

Left unilateral neglect, a dramatic condition which impairs awareness of left-sided events, has been classically reported after right hemisphere cortical lesions involving the inferior parietal region. More recently, the involvement of long range white matter tracts has been highlighted, consistent with the idea that awareness of events occurring in space depends on the coordinated activity of anatomically distributed brain regions. Damage to the superior longitudinal fasciculus (SLF), linking parietal to frontal cortical regions, or to the inferior longitudinal fasciculus (ILF), connecting occipital and temporal lobes, has been described in neglect patients. In this study, four right-handed patients with right hemisphere strokes underwent a high definition anatomical MRI with diffusion tensor imaging (DTI) sequences and a pencil and paper neglect battery of tests. We used DTI tractography to visualise the SLF, ILF and the inferior fronto-occipital fasciculus (IFOF), a pathway running the depth of the temporal lobe, not hitherto associated with neglect. Two patients with cortical involvement of the inferior parietal and superior temporal regions, but intact and symmetrical fasciculi, showed no signs of neglect. The other two patients with signs of left neglect had superficial damage to the inferior parietal cortex and white matter damage involving the IFOF. These findings suggest that superficial damage to the inferior parietal cortex per se may not be sufficient to produce visual neglect. In some cases, a lesion to the direct connections between ventral occipital and frontal regions (ie, IFOF) may contribute to the manifestation of neglect by impairing the top down modulation of visual areas from the frontal cortex.

Trans-plasma membrane electron transport in human blood platelets.

The plasma membrane redox (PMR) system is important for cell metabolism and survival; it is also crucial for blood coagulation and thrombosis. This review will give an update on the PMR system, with a particular regard to platelets, and on the role of antioxidant vitamins belonging to this system.

SVCT1 and SVCT2: key proteins for vitamin C uptake.

Vitamin C is accumulated in mammalian cells by two types of proteins: sodium-ascorbate co-transporters (SVCTs) and hexose transporters (GLUTs); in particular, SVCTs actively import ascorbate, the reduced form of this vitamin. SVCTs are surface glycoproteins encoded by two different genes, very similar in structure. They show distinct tissue distribution and functional characteristics, which indicate different physiological roles. SVCT1 is involved in whole-body homeostasis of vitamin C, while SVCT2 protects metabolically active cells against oxidative stress. Regulation at mRNA or protein level may serve for preferential accumulation of ascorbic acid at sites where it is needed. This review will summarize the present knowledge on structure, function and regulation of the SVCT transporters. Understanding the physiological role of SVCT1 and SVCT2 may lead to develop new therapeutic strategies to control intracellular vitamin C content or to promote tissue-specific delivery of vitamin C-drug conjugates.